TY - JOUR
T1 - The exosome-mediated autocrine and paracrine actions of plasma gelsolin in ovarian cancer chemoresistance
AU - Asare-Werehene, Meshach
AU - Nakka, Kiran
AU - Reunov, Arkadiy
AU - Chiu, Chen Tzu
AU - Lee, Wei Ting
AU - Abedini, Mohammad R.
AU - Wang, Pei Wen
AU - Shieh, Dar Bin
AU - Dilworth, F. Jeffrey
AU - Carmona, Euridice
AU - Le, Tien
AU - Mes-Masson, Anne Marie
AU - Burger, Dylan
AU - Tsang, Benjamin K.
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2020/2/13
Y1 - 2020/2/13
N2 - Ovarian cancer (OVCA) is the most lethal gynecological cancer, due predominantly to late presentation, high recurrence rate and common chemoresistance development. The expression of the actin-associated protein cytosolic gelsolin (GSN) regulates the gynecological cancer cell fate resulting in dysregulation in chemosensitivity. In this study, we report that elevated expression of plasma gelsolin (pGSN), a secreted isoform of GSN and expressed from the same GSN gene, correlates with poorer overall survival and relapse-free survival in patients with OVCA. In addition, it is highly expressed and secreted in chemoresistant OVCA cells than its chemosensitive counterparts. pGSN, secreted and transported via exosomes (Ex-pGSN), upregulates HIF1α–mediated pGSN expression in chemoresistant OVCA cells in an autocrine manner as well as confers cisplatin resistance in otherwise chemosensitive OVCA cells. These findings support our hypothesis that exosomal pGSN promotes OVCA cell survival through both autocrine and paracrine mechanisms that transform chemosensitive cells to resistant counterparts. Specifically, pGSN transported via exosomes is a determinant of chemoresistance in OVCA.
AB - Ovarian cancer (OVCA) is the most lethal gynecological cancer, due predominantly to late presentation, high recurrence rate and common chemoresistance development. The expression of the actin-associated protein cytosolic gelsolin (GSN) regulates the gynecological cancer cell fate resulting in dysregulation in chemosensitivity. In this study, we report that elevated expression of plasma gelsolin (pGSN), a secreted isoform of GSN and expressed from the same GSN gene, correlates with poorer overall survival and relapse-free survival in patients with OVCA. In addition, it is highly expressed and secreted in chemoresistant OVCA cells than its chemosensitive counterparts. pGSN, secreted and transported via exosomes (Ex-pGSN), upregulates HIF1α–mediated pGSN expression in chemoresistant OVCA cells in an autocrine manner as well as confers cisplatin resistance in otherwise chemosensitive OVCA cells. These findings support our hypothesis that exosomal pGSN promotes OVCA cell survival through both autocrine and paracrine mechanisms that transform chemosensitive cells to resistant counterparts. Specifically, pGSN transported via exosomes is a determinant of chemoresistance in OVCA.
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U2 - 10.1038/s41388-019-1087-9
DO - 10.1038/s41388-019-1087-9
M3 - Article
C2 - 31700155
AN - SCOPUS:85074815418
SN - 0950-9232
VL - 39
SP - 1600
EP - 1616
JO - Oncogene
JF - Oncogene
IS - 7
ER -